Linked Life Data

8114616

Source:http://linkedlifedata.com/resource/pubmed/id/8114616

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-3-25
pubmed:abstractText
Repeated, intermittent treatment of rats with amphetamine results in a sensitization of locomotor and stereotyped behaviors that is accompanied by an enhancement in stimulus-induced dopamine release. Increased phosphorylation of the neural specific calmodulin-binding protein, neuromodulin (GAP-43, B-50, F1) has been demonstrated in other forms of synaptic plasticity and plays a role in neurotransmitter release. To determine whether neuromodulin phosphorylation was altered during amphetamine sensitization, the in vivo phosphorylated state of neuromodulin was examined in rat striatum in a post hoc phosphorylation assay. Female, Holtzman rats received saline or 2.5 mg/kg amphetamine twice weekly for 5 weeks. One week after the last dose of amphetamine, rats were challenged with either 1 mg/kg or 2.5 mg/kg amphetamine or saline and the rats were sacrificed 30 min later. Purified synaptic plasma membranes were prepared in the presence of EGTA and okadaic acid to inhibit dephosphorylation, and were subsequently phosphorylated in the presence of purified protein kinase C and [gamma-32P]ATP. The protein kinase C-mediated post hoc phosphorylation of neuromodulin was significantly reduced in groups that received either acute or repeated amphetamine suggesting that neuromodulin in those groups contained more endogenous phosphate. The acute, challenge dose of amphetamine increased neuromodulin phosphorylation in the saline-treated controls but not in the repeated amphetamine-pretreated group. Anti-neuromodulin immunoblots showed no change in neuromodulin levels in any group. There was no significant change in protein kinase C activity in any treatment group. To further investigate the effect of acute amphetamine, the ability of amphetamine to alter neuromodulin phosphorylation in 32Pi-preincubated Percoll-purified rat striatal synaptosomes was examined. Amphetamine (10 microM) significantly increased phosphorylation of a 53 kDa band that migrated with authentic neuromodulin in the synaptosomes by 22% while 500 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) increased neuromodulin phosphorylation by 45%. These data suggest that one injection of amphetamine can increase neuromodulin phosphorylation in rat striatum and that this increase is maintained for at least 1 week following a repeated, sensitizing regimen of amphetamine. Since sensitization can be induced with one dose of amphetamine, it is possible that enhanced neuromodulin phosphorylation could contribute to neurochemical events leading to enhanced release of dopamine and/or behavioral sensitization.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0169-328X
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
289-98
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Phosphorylation of neuromodulin in rat striatum after acute and repeated, intermittent amphetamine.
pubmed:affiliation
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.